The Significance of Urinary Markers in the Evaluation of Diabetic Nephropathy

Tatjana Cvetković,Dušan Sokolović,Lilika Zvezdanović,Predrag Vlahović,Dušica Pavlović,Vidosava Đorđević,Gordana Kocić

doi:10.2478/v10011-008-0019-y

Abstract

The Significance of Urinary Markers in the Evaluation of Diabetic Nephropathy Oxidative stress is considered to be a unifying link between diabetes mellitus (DM) and its complications, including nephropathy (DN). The aim of this study was to determine the parameters of oxidative injury of lipids and proteins as well as the activity of ectoenzymes in the urine of DN patients. The study included 40 individuals: 10 patients with type 2 diabetes mellitus and microalbuminuria (DMT2-MIA), 10 type 2 diabetic patients with macroalbuminuria (DMT2-MAA), 10 patients with type 1 diabetes and microalbuminuria (DMT1-MIA) and 10 age- and sex-matched healthy subjects (control). In the urine we determined TBA reactive substances (TBARS), reactive carbonyl groups (RCG), and the activity of ectoenzymes N-acetyl-β-d-glucosaminidase (NAG), plasma cell differentiation antigen (PC-1), aminopeptidase N (APN) and dipeptidyl peptidase IV (DPP IV). A higher concentration of TBARS in the urine was found in DMT2-MIA and DMT1-MIA, compared to the control group (p<0.001 and P<0.05). The urine concentration of RCD shows similar results with a significant elevation in the groups with DMT2-MAA and DMT1-MIA, compared to the DMT2-MIA (p<0.001) and control group (p<0.001). Activities of NAG, APN and DPPIV were significantly higher in the urine of DMT2-MAA, compared to the control (p<0.01). The activity of PC-1 was slightly increased in that group, but not significantly. In conclusion, the level of oxidative stress markers and activities of brush border ectoenzymes in the urine may be a useful non-invasive and easily repeatable test in DN.

Highlights

Diabetes is recognized as one of the leading causes of morbidity and mortality in the world
Oxidative stress is considered to be a unifying link between diabetes mellitus (DM) and its complications, including nephropathy
Patients with diabetic nephropathy had significantly higher serum concentrations of glucose compared to the control group (p

Summary

Introduction

Diabetes is recognized as one of the leading causes of morbidity and mortality in the world. Nonenzymatic reactions between sugars and the free amino groups of proteins, lipids, and nucleic acids result in molecular dysfunction through the formation of advanced glycation end products (AGE) They are able to stimulate directly the production of extracellular matrix, inhibit its degradation and disrupt matrix-matrix and matrix-cell interactions, contributing to their profibrotic action [5]. The formation of inter- and intramolecular cross-links after the glycation of collagen leads to structural alterations, including changes in packing density and surface charge, manifested by increased stiffness, reduced thermal stability, and resistance to proteolytic digestion They can impair the binding of heparan sulfate to the extracellular matrix, which results in a loss of anionic sites and in an increase in endothelial permeability. It can be detected in almost 10–35% patients with insulin dependent and 8–25% insulin independent diabetes mellitus [8]

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